crossing96/oncoscreening huggingface dataset:
miR-4324-RACGAP1-STAT3-ESR1 feedback loop inhibits proliferation and metastasis of bladder cancer.	Considering the importance of microRNAs (miRNAs) in regulating cellular processes, we performed microarray analysis and revealed miR-4324 as one of the most differentially expressed miRNAs in bladder cancer (BCa). Then, we discovered that miR-4324 was a negative regulator of Rac GTPase activating protein 1 (RACGAP1) and that RACGAP1 functioned as an oncogenic protein in BCa. Our studies indicated that ectopic overexpression of miR-4324 in BCa cells significantly suppressed cell proliferation and metastasis and enhanced chemotherapy sensitivity to doxorubicin by repressing RACGAP1 expression. Further studies showed that estrogen receptor 1 (ESR1) increased the expression of miR-4324 by binding to its promoter, while the downregulation of ESR1 in BCa was caused by hypermethylation of its promoter. p-STAT3 induced the enrichment of DNMT3B by binding to the ESR1 promoter and then induced methylation of the ESR1 promoter. In turn, RACGAP1 induced STAT3 phosphorylation, increasing p-STAT3 expression and promoting its translocation to the nucleus. Therefore, the miR-4324-RACGAP1-STAT3-ESR1 feedback loop could be a critical regulator of BCa progression.	bladder
The prognostic role of preoperative circulating neutrophil-lymphocyte ratio in primary bladder cancer patients undergoing radical cystectomy: a meta-analysis.	BACKGROUND: Systemic inflammatory response (SIR) plays important roles in initiation, promotion and progression of tumor. However, the prognostic role of preoperative circulating neutrophil-lymphocyte ratio (NLR) (known as a marker of SIR) in human primary bladder cancer (BC) undergoing radical cystectomy (RC) remains controversial. Hence, we performed this meta-analysis to better understand the role of preoperative circulating NLR in prognosis prediction for primary BC patients undergoing RC. METHODS: We searched PubMed, Embase and EBSCO to identify the studies and computed extracted data with STATA 12.0. RESULTS: A total of 11,945 patients with BC from 18 published studies were incorporated into this meta-analysis. We found that elevated NLR was significantly associated with decreased 3-year and 5-year overall survival (OS), 1-year, 3-year and 5-year recurrence-free survival (RFS), but not with 1-year or 10-year OS, or 10-year RFS in primary BC patients who underwent RC. The results also showed that neoadjuvant chemotherapy (NAC) had a significant impact on the negative prognostic effect of NLR. In addition, high NLR significantly correlated with unfavorable clinicopathological features of BC. CONCLUSION: Elevated preoperative circulating NLR leads to an unfavorable outcome in primary BC undergoing RC, especially in patients without NAC, implicating that it might be a valuable prognostic index for these patients.	bladder
Noninvasive diagnostic imaging using machine-learning analysis of nanoresolution images of cell surfaces: Detection of bladder cancer.	We report an approach in diagnostic imaging based on nanoscale-resolution scanning of surfaces of cells collected from body fluids using a recent modality of atomic force microscopy (AFM), subresonance tapping, and machine-leaning analysis. The surface parameters, which are typically used in engineering to describe surfaces, are used to classify cells. The method is applied to the detection of bladder cancer, which is one of the most common human malignancies and the most expensive cancer to treat. The frequent visual examinations of bladder (cytoscopy) required for follow-up are not only uncomfortable for the patient but a serious cost for the health care system. Our method addresses an unmet need in noninvasive and accurate detection of bladder cancer, which may eliminate unnecessary and expensive cystoscopies. The method, which evaluates cells collected from urine, shows 94% diagnostic accuracy when examining five cells per patient's urine sample. It is a statistically significant improvement (P < 0.05) in diagnostic accuracy compared with the currently used clinical standard, cystoscopy, as verified on 43 control and 25 bladder cancer patients.	bladder
A delay ≥8 weeks to neoadjuvant chemotherapy before radical cystectomy increases the risk of upstaging.	OBJECTIVES: To investigate delays to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) and their effect on outcomes in a large national registry of patients with localized muscle invasive bladder cancer. PATIENTS AND METHODS: Within the National Cancer Database (2004-2014), we identified 2,227 patients who underwent NAC and RC for cT2-T4aN0M0 urothelial carcinoma of the bladder. Times from diagnosis to treatments were tested for association with overall survival and pathologic outcomes, using Cox models, and restricted cubic splines regression. RESULTS: Median times from diagnosis to NAC and RC were 39 days (interquartile range: 26-56) and 155 days (interquartile range: 131-185), respectively. Time to NAC and time to RC were not associated with overall survival in the complete cohort, as well as in subgroups of responders and nonresponders to NAC. Overall, 916 patients (41%) were upstaged after RC, including 485 patients (22%) with positive lymph nodes. We identified delay to NAC ≥8 weeks as a significant cut-off point to predict the risk of upstaging in multivariable analysis (odds ratio: 1.27; 95% confidence interval: 1.02-1.59; P = 0.031). Black race, Medicaid insurance, and academic facilities were associated with a higher risk of delayed treatment. CONCLUSION: After diagnosis of muscle invasive bladder cancer, NAC should be initiated as soon as possible and no more than 8 weeks to prevent upstaging. There is no evidence to support avoiding NAC due to concerns of delayed RC that was generated from surgery alone studies, as long as RC is performed within 7 months from initial diagnosis.	bladder
Gemcitabine/cisplatin versus methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive bladder cancer: A systematic review and meta-analysis.	OBJECTIVE: The objective of this study was to perform a systematic review and meta-analysis to evaluate the two most commonly used chemotherapy regimens gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin/adriamycin, and cisplatin (MVAC) regimens for muscle-invasive bladder cancer (MIBC) patients. METHODS: We searched for all studies investigating GC and MVAC for MIBC patients in PubMed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed. RESULTS: Our searches identified 13 studies among 2174 patients. In the meta-analysis, the pathological complete response to GC regimens was superior to MVAC regimens. No significant difference in pathological partial response was found between the two groups. GC regimens were associated with a significant decrease risk in Grade 3-4 neutropenia, mucositis, and febrile neutropenia, but a significant increase risk in Grade 3-4 thrombocytopenia. There was no significant difference in overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) when compared GC regimens to MVAC regimens. CONCLUSIONS: GC regimens significantly improved pathological complete response compared to MVAC regimens. GC regimens were associated with a significant decrease risk in Grade 3-4 neutropenia, mucositis, and febrile neutropenia, but a significant increase risk in Grade 3-4 thrombocytopenia. There was no significant difference in OS, DSS, and DFS when compared the two regimens.	bladder
Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder.	Muscle-invasive urothelial carcinoma of the urinary bladder (UCB) often recurs following radical cystectomy (RC). An altered expression of sex-steroid hormone receptors has been associated with oncological outcomes of UCB and may represent therapeutic targets. Here the expression of different hormone receptors was measured on mRNA levels in patients treated by RC and associated with outcomes. Androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in RC samples of 87 patients with a median age of 66 (39-88) years. Univariate and multivariate analyses were performed to test associations with pathological and clinical characteristics as well as recurrence-free (RFS) and disease-specific survival (DSS). AR mRNA expression was lower in comparison with ESR1 and PGR expression (p < 0.0001). In univariate analysis, high expression levels of AR were associated with reduced RFS (HR 2.8, p = 0.015) and DSS (HR 2.8, p = 0.010). High AR mRNA expression and a positive lymph node status were independent predictors for reduced RFS (HR 2.5, p = 0.0049) and DSS (HR 3.4, p = 0.009). In patients with low AR mRNA expression, an increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS. High expression levels of AR are significantly associated with adverse outcome in patients with muscle-invasive UCB following RC. ESR1 and PGR expression status can further stratify patients with low AR expression into subgroups with significantly reduced RFS and DSS. Therapeutic targeting of AR may influence outcomes in patients with UCB.	bladder
Inhibition of TPL2 by interferon-α suppresses bladder cancer through activation of PDE4D.	BACKGROUND: Drugs that inhibit the MEK/ERK pathway have therapeutic benefit in bladder cancer treatment but responses vary with patients, for reasons that are still not very clear. Interferon-α (IFN-α) is also used as a therapeutic agent for bladder cancer treatment but the response rate is low. It was found that IFN-α could enhance the cytotoxic effect of MEK inhibition. However, the potential mechanisms of that are still unclear. Understanding of the cross-talk between the IFN-α and MEK/ERK pathway will help enhance the efficacy of IFN-α or MEK inhibitors on bladder cancer. METHODS: Immunoprecipitation and pull-down assay were used to reveal the formation of signaling complex. The protein expressions were detected by western blot and immunohistochemistry. The cAMP level, Phosphodiesterase 4D (PDE4D) activity and Prostaglandin E(2) (PGE(2)) concentration in cells, serum and tissues were detected by enzyme-linked immunosorbent assay. The role of PDE4D in bladder tumorigenesis in vivo was examined by the xenograft model. Tissue microarray chips were used to investigate the prognostic roles of PDE4D and tumor progression locus 2 (TPL2) in bladder cancer patients. RESULTS: IFN-α down-regulated the cyclooxygenase-2 (COX-2) expression in bladder cancer cells through the inhibition of TPL2/NF-κB pathway; IFN-α also inhibited COX-2 expression by suppressing cAMP signaling through TPL2-ERK mediated PDE4D activity. Reduction of the intracellular cAMP level by PDE4D potentiated the antitumor effect of IFN-α against bladder cancer in vitro and in vivo. Further analysis of clinical samples indicated that low PDE4D expression and high level of TPL2 phosphorylation were correlated to the development and poor prognosis in bladder cancer patients. CONCLUSIONS: Our data reveal that IFN-α can exert its antitumor effect through a non-canonical JAK-STAT pathway in the bladder cancer cells with low activity of IFN pathway, and the TPL2 inhibition is another function of IFN-α in the context of bladder cancer therapy. The antitumor effects of IFN-α and MEK inhibition also depend on the PDE4D-mediated cAMP level in bladder cancer cells. Suppression of the TPL2 phosphorylation and intracellular cAMP level may be possible therapeutic strategies for enhancing the effectiveness of IFN-α and MEK inhibitors in bladder cancer treatment.	bladder
(89)Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer.	Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade is effective in a subset of patients with several tumor types, but predicting patient benefit using approved diagnostics is inexact, as some patients with PD-L1-negative tumors also show clinical benefit(1,2). Moreover, all biopsy-based tests are subject to the errors and limitations of invasive tissue collection(3-11). Preclinical studies of positron-emission tomography (PET) imaging with antibodies to PD-L1 suggested that this imaging method might be an approach to selecting patients(12,13). Such a technique, however, requires substantial clinical development and validation. Here we present the initial results from a first-in-human study to assess the feasibility of imaging with zirconium-89-labeled atezolizumab (anti-PD-L1), including biodistribution, and secondly test its potential to predict response to PD-L1 blockade (ClinicalTrials.gov identifiers NCT02453984 and NCT02478099). We imaged 22 patients across three tumor types before the start of atezolizumab therapy. The PET signal, a function of tracer exposure and target expression, was high in lymphoid tissues and at sites of inflammation. In tumors, uptake was generally high but heterogeneous, varying within and among lesions, patients, and tumor types. Intriguingly, clinical responses in our patients were better correlated with pretreatment PET signal than with immunohistochemistry- or RNA-sequencing-based predictive biomarkers, encouraging further development of molecular PET imaging for assessment of PD-L1 status and clinical response prediction.	bladder
Targeted regulation by ROCK2 on bladder carcinoma via Wnt signaling under hypoxia.	Bladder cancer is frequently occurred in urinary system and has complicated pathogenesis factors including both genetics and environmental factors that have not been fully illustrated. Hypoxia can further induce tumor progression. ROCK2 has abnormal expression in various tumors but its expression or functional role in bladder cancer have not been illustrated. In vitro cultured bladder cancer cell line T24 was randomly assigned into control group, hypoxia group (prepared under hypoxic culture), and ROCK2 siRNA group (transfected with ROCK2 siRNA after hypoxia treatment). Real-time PCR and Western bot measured ROCK2 expression. MTT assay tested cell proliferation, and cell migration was quantified. Cell apoptosis was measured by caspase3 activity assay kit and Transwell chamber measured cell migration. Western blot quantified expressional change of HIF-1α and E-cadherin, and Wnt signal pathway proteins including Wnt4, and β-catenin. ROCK2 is up-regulated in bladder cancer T24 cells under hypoxia, and can facilitate cell proliferation, migration and invasion, inhibited Caspase3 activity, enhanced HIF-1α expression, decreased E-cadherin expression, and up-regulated Wnt4 and β-catenin (p< 0.05 comparing to hypoxia group). Under hypoxia conditions, ROCK2 can facilitate apoptosis of bladder cancer cells via modulating Wnt signal pathway, inhibit cell proliferation, migration, invasion or formation of epithelial mesenchymal transition (EMT).	bladder
TROY expression is associated with pathological stage and poor prognosis in patients treated with radical cystectomy.	BACKGROUND: New biomarkers may help us provide individualized prognosis and allow risk-stratified clinical decision making about radical treatment. OBJECTIVES: This study aimed to determine the tumor necrosis factor of receptor superfamily 19 (TROY) expression in urothelial carcinoma and its relationship to clinicopathological findings. METHODS: Immunohistochemical staining for TROY was carried out in 136 archival radical cystectomy specimens with immunoreactivity being stratified on a 0-9 scale. Expression scores for TROY were further stratified into negative (score 0) and positive (score 1 or greater). Median age was 65 years, and the median follow-up period was 50.7 months. RESULTS: Expression of TROY was significantly associated with the pathological stage (p= 0.019) and expression of nestin (p= 0.013). Log-rank tests indicated that expression of TROY was significantly associated with disease progression and cancer-specific mortality (p= 0.044 and 0.008, respectively). In multivariate Cox regression analysis, lymph node status was the only independent prognostic factor for disease progression and cancer-specific survival. Expression of TROY was a marginal prognostic factor for cancer-specific survival. CONCLUSIONS: TROY may therefore be a new molecular marker to aid in identifying and selecting patients undergoing radical cystectomy who could potentially benefit from multimodal treatment.	bladder
Premature Mortality Due to Malignancies of the Kidney and Bladder in Japan, 1980-2010.	BACKGROUND: In the present study, we examined the trends of premature mortality due to kidney and bladder cancers among the Japanese population from 1980 through 2010. METHODS: Mortality data were obtained from the World Health Organization mortality database. Years of life lost (YLL) was estimated using Japanese life tables. Average lifespan shortened (ALSS) was calculated and defined as the ratio of years of life lost relative to the expected lifespan. RESULTS: Over the study period, the age-standardized rates to the World Standard Population for deaths from kidney and bladder cancers were stable. The average years of life lost (AYLL) measure shows decreases of about 4 and 6 years of life for kidney cancer in men and women, respectively, and decreases of about 2 years of life for bladder cancer in both sexes. The ALSS shows that patients with kidney cancer lost 21.0% and 24.7% of their lifespan among men and women in 1980, whereas respective losses were 15.3% and 15.8% in 2010. Also, patients with bladder cancer on average lost 13.5% in men and 14.2% in women in 1980 and 10.8% in men and 11.1% in women in 2010. CONCLUSIONS: Our study shows favorable trends in premature mortality for kidney and bladder cancers in Japan over a 30-year period; however, patients with bladder cancer on average lost a smaller proportion of their lifespan compared to those with kidney cancer. The development of a novel ALSS measure is convenient in examination of the burden of premature mortality over time.	bladder
LncRNA miR143HG suppresses bladder cancer development through inactivating Wnt/β-catenin pathway by modulating miR-1275/AXIN2 axis.	Although increasing long noncoding RNAs (lncRNAs) have been identified by high-throughput sequencing, their functions in human cancer remain largely unknown. The function of lncRNA miR143HG has not been explored before. In the present study, we found that miR143HG expression was significantly downregulated in bladder cancer tissues (BCa) compared with normal tissues. We showed that miR143HG high expression was associated with a high survival rate in BCa patients. Gain-of-function assays demonstrated that miR143HG overexpression suppressed the proliferation, arrested cell cycle progression, and attenuated migration and invasion of BCa cells in vitro. In vivo assay illustrated that ectopic expression of miR143HG inhibited BCa growth in vivo. Mechanistically, miR143HG was identified to inhibit the level of miR-1275, whereas miR-1275 directly targeted AXIN2, a negative regulator of the Wnt/β-catenin pathway. Restoration of miR-1275 or knockdown of AXIN2 significantly rescued the proliferation, migration, and invasion abilities of BCa cells. In summary, our findings demonstrated that miR143HG/miR-1275/AXIN2 axis regulates BCa development by modulating the Wnt/β-catenin pathway.	bladder
Cancer stem cells as a therapeutic target in bladder cancer.	Bladder cancer is one of the most prevalent genitourinary cancers responsible for about 150,000 deaths per year worldwide. Currently, several treatments, such as endoscopic and open surgery, appended by local or systemic immunotherapy, chemotherapy, and radiotherapy are used to treat this malignancy. However, the differences in treatment outcome among patients suffering from bladder cancer are considered as one of the important challenges. In recent years, cancer stem cells, representing a population of undifferentiated cells with stem-cell like properties, have been eyed as a major culprit for the high recurrence rate in superficial papillary bladder cancer. Cancer stem cells have been reported to be resistant to conventional treatments, such as chemotherapy, radiation, and immunotherapy, which induce selective pressure on tumoral populations resulting in selection and growth of the resistant cells. Therefore, targeting the therapeutic aspects of cancer stem cells in bladder cancer may be promising. In this study, we briefly discuss the biology of bladder cancer and then address the possible relationship between molecular biology of bladder cancer and cancer stem cells. Subsequently, the mechanisms of resistance applied by cancer stem cells against the conventional therapeutic tools, especially chemotherapy, are discussed. Moreover, by emphasizing the biomarkers described for cancer stem cells in bladder cancer, we have provided, described, and proposed targets on cancer stem cells for therapeutic interventions and, finally, reviewed some immunotargeting strategies against bladder cancer stem cells.	bladder
MR Imaging of the Urinary Bladder: Added Value of PET-MR Imaging.	MR imaging has been increasingly getting attention for the evaluation of bladder cancer. Recent studies have been promising for the staging performance of MR imaging in the bladder cancer, although its specific role has not been established yet. Additionally, the use of hybrid imaging combining PET with MR imaging could have the potential to increase its accuracy, although more research studies are needed.	bladder
Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration.	Cancer immunotherapy has emerged as an effective therapy in a variety of cancers. However, a key challenge in the field is that only a subset of patients who receive immunotherapy exhibit durable response. It has been hypothesized that host genetics influences the inherent immune profiles of patients and may underlie their differential response to immunotherapy. Herein, we systematically determined the association of common germline genetic variants with gene expression and immune cell infiltration of the tumor. We identified 64,094 expression quantitative trait loci (eQTLs) that associated with 18,210 genes (eGenes) across 24 human cancers. Overall, eGenes were enriched for their being involved in immune processes, suggesting that expression of immune genes can be shaped by hereditary genetic variants. We identified the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene as a pan-cancer type eGene whose expression levels stratified overall survival in a subset of patients with bladder cancer receiving anti-PD-L1 (atezolizumab) therapy. Finally, we identified 103 gene signature QTLs (gsQTLs) that were associated with predicted immune cell abundance within the tumor microenvironment. Our findings highlight the impact of germline SNPs on cancer-immune phenotypes and response to therapy; and these analyses provide a resource for integration of germline genetics as a component of personalized cancer immunotherapy.	bladder
Lung Involvement in Chronic Schistosomiasis with Bladder Squamous Cell Carcinoma.	We report a case of chronic Schistosoma haematobium infection with pseudometastatic pulmonary nodules and high-grade squamous cell carcinoma in a 30-year-old man in Mali. Lung biopsies revealed chronic pulmonary involvement of S. haematobium and ruled out lung metastases.	bladder